title: Electron-induced degradation of 8-bromo-2'-deoxyadenosine 3',5'-diphosphate, a DNA radiosensitizing nucleotide.
abstract: The phosphodiester bond cleavage in 8-bromo-2'-deoxyadenosine 3',5'-diphosphate (BrdADP), as a model of electron induced single strand break (SSB) in labeled DNA, was investigated at the B3LYP/6-31++G(d,p) level of theory both in the gas phase and in water solution. Barrier-free and highly exergonic, especially in water solution (-2.83 eV), release of the bromide anion due to electron attachment confirms radiosensitizing properties of 8-bromoadenine. Thermodynamically (-19 kcal/mol) and kinetically (barrier of 10-13 kcal/mol) feasible hydrogen atom transfer from the C3' or C5' sites of the deoxyribose moiety to the C8 center of adenine radical is followed by a relatively low (14-18 kcal/mol) activation barrier O-P bond cleavage at either the 3'- or the 5'-site. The C5' radical may also stabilize via the formation of 5',8-cycloadenosine. The latter process has favorable thermodynamic and kinetic characteristics, which makes the O-P bond breakage at the 5'-site highly unlikely. Thus, the O-P cleavage reaction, being an equivalent of SSB in DNA labeled with 8-bromoadenine, should lead to the formation of cyclic ketone, which if identified in a radiolytic experiment, would confirm the mechanism proposed in the current study.
authors.affiliation: Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Chomicz
authors.forename: Jerzy
authors.initials: J
authors.lastname: Leszczynski
authors.forename: Janusz
authors.initials: J
authors.lastname: Rak
mesh_terms: D004247:DNA / Q000737:chemistry; D003839:Deoxyadenosines / Q000737:chemistry*; D004583:Electrons; D007700:Kinetics; D008958:Models, Molecular; D011789:Quantum Theory; D011838:Radiation-Sensitizing Agents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D003839:Deoxyadenosines; D011838:Radiation-Sensitizing Agents; C042464:8-bromo-2'-deoxyadenosine; D004247:DNA